Neurodegenerative diseases in which neuronal cells degenerate bring about a deterioration of cognitive functions. A variety of diseases and neurological deficiencies may bring about the degeneration of neuronal cells among them Alzheimer's disease, Huntington disease or chorea, hypoxia or ischemia caused by stroke, cell death caused by epilepsy, amyotrophic lateral sclerosis, mental retardation etc., as well as neurodegenerative changes resulting from aging.
Vasoactive intestinal peptide (VIP) is a 28 amino acid regulatory peptide which exhibits neurotransmitter and hormonal roles. VIP has a discrete distribution in the central nervous system (CNS), with highest levels in the cerebral cortex, hypothalamus, amygdala and corpus striatum. Accumulated evidence suggest the involvement of VIP in a multitude of neuronal functions among them: changes in membrane potential, modulation of muscarinic excitation, promotion of survival of electrically blocked neurons.sup.(1), maintenance of neural integrity.sup.(2), development of neonatal behavior in rats.sup.(3), rescue from neural death caused by HIV envelope protein. A VIP-receptor antagonist caused spatial learning impairment in rats which was attenuated by co-treatment with VIP, indicating a possible role for VIP in the process of learning.sup.(4).
There is conflicting evidence concerning the role of VIP in dementia in general and in Alzheimer's disease in particular. A large body of evidence suggests no such involvement. Rosor et at found no changes in VIP in cerebral cortex of brains obtained from patients suffering from senile dementia of the Alzheimer's type as compared to controIs.sup.(5). Other investigators found no variance in VIP measurement between Alzheimer's patients and controls.sup.(6,7,8), and no correlation was found between the degree of dementia and the concentration of VIP in the cerebrospinal fluid.sup.(9).
In contrast, a study of immunoreactivity of VIP in Alzheimer's and control brains showed a significant reduction of VIP immunoreactivity in the cerebral cortex especially in the insular and angulate cortex of Alzheimer's patients.sup.(10). However, it has never been determined whether this reduction was the cause or rather the result of the Alzheimer's deterioration of the cerebral cortex.